(6R)-7t-amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-oxa-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester | 66429-65-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6R)-7t-amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-oxa-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• 英文别名: benzhydryl (6R,7S)-7-amino-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 66429-65-0
• 化学式: C₂₃H₂₂N₆O₄S
• 分子量: 478.531
• InChiKey: NLYDBKCBWQGRIA-DYESRHJHSA-N

物化性质

• 沸点：
  717.0±70.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.41
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  125.46
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (6R)-7t-amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-oxa-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 在 吡啶 、 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.66h， 生成 (6R,7S)-7-[2-[(Z)-Hydroxyimino]-2-(4-methanesulfonylamino-phenyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-oxa-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  1-Oxacephalosporins: enhancement of .beta.-lactam reactivity and antibacterial activity

  摘要：

  The effect of replacement of sulfur in the cephem nucleus by oxygen upon the beta-lactamase stability, infrared carbonyl frequency of the beta-lactam ring, and antibacterial activity was investigated. The replacement reduced the stability of beta-lactam compounds to beta-lactamases, increased the IR frequencies, and enhanced the intrinsic antibacterial activity against bacterial strains without beta-lactamase. The instability of 1-oxacephalosporins to beta-lactamases, in other words, high reactivity to the enzymes, seemed to be due to the enhanced chemical reactivity of their beta-lactam rings which was indicated by their higher IR beta-lactam carbonyl frequencies. Based on a view that acylation of the enzyme by beta-lactam compounds occurred in both cases of beta-lactamase hydrolysis and target enzyme inhibition, the suggestion was made that one of the factors which conferred the higher intrinsic antibacterial activity on 1-oxacephalosporins was their high reactivity to the target enzyme(s), as was the case with beta-lactamases.

  DOI：

  10.1021/jm00133a018
• 作为产物：
  描述：

  拉氧头孢钠中间体 2 在 盐酸 、 吡啶硼烷 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以94%的产率得到(6R)-7t-amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-oxa-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Aoki, Tsutomu; Nagata, Wataru, Heterocycles, 1989, vol. 28, # 2, p. 687 - 695

  摘要：

  DOI：

文献信息

• Synthesis and substituent effects on antibacterial activity, alkaline hydrolysis rates, and infrared absorption frequencies of some cephem analogs related to latamoxef (moxalactam)
  作者：Masayuki Narisada、Tadashi Yoshida、Mitsuaki Ohtani、Kiyoshi Ezumi、Mamoru Takasuka

  DOI：10.1021/jm00365a006

  日期：1983.11

  Relationships between intrinsic antibacterial activity and beta-lactam reactivity of 7 beta-[(4-hydroxyphenyl)acetyl]amino- and 7 beta-[(4-hydroxyphenyl)malonyl]amino derivatives of 1-oxa- and 1-thiacephems, with or without the 7 alpha-methoxy group (1-8), were investigated in order to clarify the enhanced antibacterial activity of latamoxef disodium (1). Substituent effects of a carbon atom at the 1- and

  1-oxa-和1-thiacephems的7个β-[（4-羟苯基）乙酰基]氨基和7个β-[（4-羟苯基）丙二酰基]氨基衍生物的固有抗菌活性与β-内酰胺反应性之间的关系为了阐明Latamoxef二钠（1）增强的抗菌活性，对不含7个α-甲氧基（1-8）的化合物进行了研究。还通过使用外消旋的1-碳嘧啶9和7个α-甲基-1-氧嘧啶10研究了碳原子在1-和7位的取代基作用。还描述了2-8和10的合成。衍生自（4-羟苯基）乙酸的O-苄氧基羰基衍生物的酰氯和（4-羟苯基）丙二酸的对甲氧基苄基衍生物顺利地引入了这些侧链。在16位立体定向中共轭添加二甲基cup酸锂到醌系统，提供了7个α-甲基用于合成10。合成敏感革兰氏阴性菌株（大肠杆菌NIHJ JC-2）的log（1 / C）平均值和肺炎克雷伯菌（Klebsiella pneumoniae SRL-1）被认为是固有的抗菌活性。β-内酰胺环的化学反应性是通过在pH
• Practical procedure for epimerization of 7α-amino-1-oxacephems to 7β-amino epimers
  作者：T. Aoki、N. Haga、Y. Sendo、T. Konoike、M. Yoshioka、W. Nagata

  DOI：10.1016/s0040-4039(01)80812-1

  日期：——

  7α-Amino-1-oxacephems can be epimerized to their 7β-amino epimers by treatment with chloral to give Schiff bases, followed by dehydrochlorination with Hünig base, borohydride reduction, and hydrolysis.

  通过用氯醛处理可将7α-Amino-1-oxacephems与其7β-氨基差向异构体异构化，生成Schiff碱，然后用Hünig碱进行脱氯化氢，硼氢化物还原和水解。
• A new determination of the absolute configuration of the chiral amine
  作者：Yoshimitsu Nagao、Masahiro Yagi、Takao Ikeda、Eiichi Fujita

  DOI：10.1016/s0040-4039(00)86786-6

  日期：1982.1

  A new method for assignment of the absolute configuration of the asymmetric carbon atom attached to an amino or imino group using rac.-3-hexadecanoyl-4-methoxycarbonyl-1,3-thiazolidine-2-thione (rac.-HDMTT) (4) is described.

  一种使用rac分配与氨基或亚氨基连接的不对称碳原子的绝对构型的新方法。-3-十六烷酰基-4-甲氧羰基-1,3-噻唑烷-2-硫酮（外消旋。-HDMTT）（4）进行说明。
• 一种拉氧头孢钠的合成方法
  申请人：济南康和医药科技有限公司

  公开号：CN110804635B

  公开（公告）日：2021-08-17

  本发明涉及一种拉氧头孢钠的合成方法，具体为氧头孢母核1与1‑甲基‑5巯基四氮唑钠盐作用得到化合物2，之后经过脱保护得到化合物3，化合物3上甲氧基、7位侧链得到化合物5，随后化合物5最终脱保护得到高纯度拉氧头孢钠。本发明提供的方法收率高、条件温和、环境友好；用酶进行脱保护和缩合反应，避免使用高毒性、高腐蚀性试剂；以高收率得到高纯度的拉氧头孢钠。
• Synthetic studies on β-lactam antibiotics. Part 10. Synthesis of 7β-[2-carboxy-2-(4-hydroxyphenyl)acetamido]-7.alpha.-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-1-oxa-1-dethia-3-cephem-4-carboxylic acid disodium salt (6059-S) and its related 1-oxacephems
  作者：Masayuki Narisada、Tadashi Yoshida、Hiroshi Onoue、Mitsuaki Ohtani、Tetsuo Okada、Teruji Tsuji、Ikuo Kikkawa、Nobuhiro Haga、Hisashi Satoh

  DOI：10.1021/jm00193a001

  日期：1979.7